Stapled Peptides with Improved Potency and Specificity That Activate p53
ACS Chemical Biology2012Vol. 8(3), pp. 506–512
Citations Over TimeTop 10% of 2012 papers
Christopher J. Brown, Soo Tng Quah, J.G.Y. de Jong, Amanda M. Goh, Poh Cheang Chiam, Kian Hoe Khoo, Meng Ling Choong, May A. Lee, Larisa Yurlova, Kourosh Zolghadr, Thomas L. Joseph, Chandra Verma, David P. Lane
Abstract
By using a phage display derived peptide as an initial template, compounds have been developed that are highly specific against Mdm2/Mdm4. These compounds exhibit greater potency in p53 activation and protein-protein interaction assays than a compound derived from the p53 wild-type sequence. Unlike Nutlin, a small molecule inhibitor of Mdm2/Mdm4, the phage derived compounds can arrest cells resistant to p53 induced apoptosis over a wide concentration range without cellular toxicity, suggesting they are highly suitable for cyclotherapy.
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